Exercise training reverses inflammation and muscle wasting after tobacco smoke exposure

Am J Physiol Regul Integr Comp Physiol. 2018 Mar 1;314(3):R366-R376. doi: 10.1152/ajpregu.00316.2017. Epub 2017 Nov 1.

Abstract

Long-term cigarette smoking induces inflammatory processes in the pulmonary system that are suggested to "spill over" into systemic inflammation. Regular exercise has been shown to have anti-inflammatory properties. The aim of the study was to investigate the effects of therapeutic exercise on inflammation and muscle wasting in smoke-exposed mice. C57BL/6J mice ( n = 30) were separated into three groups to receive either 1) no specific treatment (control group), 2) 8-mo exposure to cigarette smoke [smoke-exposed (SE) group], or 3) 8 mo of cigarette smoke combined with exercise training during the last 2 mo (SEex group). The inflammatory status was analyzed by quantifying levels of various plasma proteins using multiplex ELISA and detection of lymphocyte surface markers by flow cytometry. Muscle tissue was analyzed by histological techniques and measurements of RNA/protein expression. SE led to decreased maximal O2 uptake (V̇o2max) and maximal running speed ( Vmax), which was reversed by exercise ( P < 0.05). Expression of ICAM-1, VCAM-1, and CD62L on T cells increased and was reversed by exercise ( P < 0.05). Similarly, SE induced an increase of various inflammatory cytokines, which were downregulated by exercise. In muscle, exercise improved the structure, oxidative capacity, and metabolism by reducing ubiquitin proteasome system activation, stimulating insulin-like growth factor 1 expression, and the SE-induced inhibition of mammalian target of rapamycin signaling pathway ( P < 0.05). Exercise training reverses smoke-induced decline in exercise capacity, systemic inflammation, and muscle wasting by addressing immune-regulating, anabolic, and metabolic pathways.

Keywords: chronic obstructive pulmonary disease; cytokines; exercise capacity; immune system; lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism
  • Cigarette Smoking / adverse effects*
  • Cytokines / blood
  • Disease Models, Animal
  • Exercise Therapy / methods*
  • Exercise Tolerance
  • Inflammation / blood
  • Inflammation / etiology
  • Inflammation / physiopathology
  • Inflammation / therapy*
  • Inflammation Mediators / blood
  • Male
  • Mice, Inbred C57BL
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscular Atrophy / blood
  • Muscular Atrophy / etiology
  • Muscular Atrophy / physiopathology
  • Muscular Atrophy / therapy*
  • Oxidative Stress
  • Proteasome Endopeptidase Complex / metabolism
  • Quadriceps Muscle / metabolism
  • Quadriceps Muscle / pathology
  • Quadriceps Muscle / physiopathology*
  • Recovery of Function
  • Signal Transduction
  • Smoke / adverse effects*
  • T-Lymphocytes / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Time Factors

Substances

  • Cell Adhesion Molecules
  • Cytokines
  • Inflammation Mediators
  • Muscle Proteins
  • Smoke
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Proteasome Endopeptidase Complex